Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability‐based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array‐based comparative genomic hybridization. Analyzing clinical blood samples from metastatic (n = 20) and nonmetastatic (n = 6) cancer patients in parallel with CellSearch® system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM‐negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as “liquid biopsies.”
Cancer cells from solid tumors can enter the circulatory system and survive to subsequently form distant metastases. The CellSearch® system (Menarini-Silicon Biosystems, Huntingdon Valley, PA) was the first, FDA-cleared system that provided a reliable tool for the investigation of circulating tumor cells (CTCs), which have been shown to be strongly associated with poor survival and therapy failure. Since that time, a number of new technologies have been introduced to improve CTC detection and/or isolation for further characterization. The continued and growing interest in the "liquid biopsy" field has spurred the development of numerous different CTC technologies. However, selecting the most appropriate CTC platform for individual applications can be challenging. No consensus has yet been reached in the community regarding which liquid biopsy technology is optimal. Here, we introduce the Parsortix™ Cell Separation System (ANGLE North America, Inc., King of Prussia, PA), a microfluidic based technology that captures rare cells based on size and deformability, offers reproducibly high capture efficiency, and produces highly enriched, viable (viability dependent on preservative used) CTCs that are amenable to a multitude of downstream analyses, including the isolation and interrogation of single cells.
These preliminary results indicate that adolescents with BD treated with lamotrigine demonstrated less amygdalar activation when viewing negative stimuli as depressive symptoms improved. Larger controlled studies are needed to confirm these findings.
Our findings suggest that DLPFC NAA/Cr ratios cannot be used as a trait marker for BD. Although we did not find decreased DLPFC NAA/Cr ratios in children and adolescents with BD, it is still possible that such levels begin to decrease after longer durations of illness into adulthood. Longitudinal neuroimaging studies of patients with BD accounting for developmental and treatment factors are needed to further clarify the neurodegenerative aspects of BD.
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